How to turn a mint into catmint: the origins of specialised metabolism

如何将薄荷变成猫薄荷：专门新陈代谢的起源

• 批准号: BB/V006452/1
• 负责人: Benjamin Lichman
• 金额: $ 66.68万
• 依托单位: University of York
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2021
• 资助国家: 英国
• 起止时间: 2021 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FV006452%2F1
• 关键词: How; turn; mint; into; catmint

As they cannot move, plants must find innovative ways to defend themselves and interact with their environment. The solution that many plants have come up with is to make unique chemicals with a particular function, such as repelling insects or providing protection from the sun's UV rays. Many of these chemicals, known as natural products, are used by humankind for fragrances and medicines. Finding out how plants have evolved to make these chemicals will help us understand a core aspect of how plants adapt to the environment. It may also provide us with lessons for how to make similar natural product-like chemicals in the future.We are investigating how plants evolve to make new chemicals. Our research focuses on catmint, also known as catnip or Nepeta. Catmint is famous for its euphoric effects on cats, which is the result of a chemical produced by catmint called nepetalactone. Catmint is part of the mint family, which includes plants such as lavender, oregano and, of course, mint. However, catmint has evolved uniquely amongst the mints to make nepetalactone. We will try to find out exactly how a mint has evolved into catmint: how did Nepeta evolve to make this unique compound?To investigate this we will first obtain genome sequences of different catmint species and close relatives. A genome sequence is essentially a collection of an organism's genes, and is often considered a DNA "blueprint" or a set of instructions for an organism. The genomes will show us the genes that are involved making nepetalactone in the different species, and we can also see how genes are positioned on the genome relative to each other. We can perform calculations to estimate what the genes of catmint ancestors looked like many millions of years ago. This allows us to resurrect and test these ancient genes in the lab to find out what chemicals the ancestors of catmint could make.Once we have enough genomes to perform good and robust analyses, we will focus on genes called NEPS that are responsible for making nepetalactone. These genes went through remarkable rapid changes in the ancestor of catmint. We will resurrect these ancient genes at important time points in catmint evolutionary history and test them in the lab to see how their behaviour has changed. We will be looking out for what changes occurred for them to transform from a normal gene to one that can make nepetalactone.However, plants need many genes to make chemicals like nepetalactone, not just one. We must therefore extend this ancestral analysis to multiple genes, and we plan to test a variety of genes simultaneously to recreate an "ancestral metabolism" and so determine what chemicals the ancestors of catmint could make. We will also try to work out where in the genomes the genes were positioned during evolution. Genes appear to jump around in genomes as they evolve and we hope to discover why that happens by comparing the gene's behaviours with the genome locations.Conducting all of this research will allow us to answer when and how catmint gained the ability to make nepetalactone. This, in turn, will provide wider lessons for how plants make new chemicals and how their genes and genome evolve to adapt to the environment. Plants are nature's green chemists: learning how plants make useful chemicals could help us to make our own plant-inspired chemicals in an environmentally friendly manner.

由于它们不能移动，植物必须找到创新的方法来保护自己并与环境互动。许多植物想出的解决方案是制造具有特殊功能的独特化学物质，例如驱赶昆虫或提供对太阳紫外线的保护。其中许多化学物质被称为天然产品，被人类用来制作香水和药物。找出植物是如何进化来制造这些化学物质的，将有助于我们了解植物如何适应环境的一个核心方面。它还可能为我们提供未来如何制造类似天然产品的化学物质的经验教训。我们正在研究植物如何进化来制造新的化学物质。我们的研究重点是薄荷，也被称为猫薄荷或尼泊尔薄荷。薄荷对猫咪的愉悦作用是出了名的，这是由薄荷产生的一种名为内酯的化学物质的结果。薄荷是薄荷家族的一部分，包括薰衣草、牛至等植物，当然还有薄荷。然而，薄荷在薄荷中进化得独一无二，可以制造奈派内酯。我们将试图找出薄荷是如何进化成薄荷的：尼泊尔是如何进化成这种独特的化合物的？为了研究这一点，我们首先要获取不同薄荷物种和近亲的基因组序列。基因组序列本质上是一个有机体基因的集合，通常被认为是一个生物体的DNA“蓝图”或一套指令。基因组将向我们展示在不同物种中参与制造奈派内酯的基因，我们还可以看到基因在基因组上的相对位置。我们可以通过计算来估计数百万年前薄荷祖先的基因是什么样子的。这使我们能够在实验室中复活和测试这些古老的基因，以找出薄荷的祖先可以制造什么化学物质。一旦我们有足够的基因组进行良好和强大的分析，我们将专注于被称为NNs的基因，这些基因负责制造奈派内酯。这些基因在薄荷的祖先身上经历了惊人的快速变化。我们将在薄荷进化史上的重要时间点复活这些古老的基因，并在实验室中对它们进行测试，看看它们的行为发生了怎样的变化。我们将关注它们发生了什么变化，使它们从正常的基因转变为可以产生内酯的基因。然而，植物需要许多基因来制造内酯这样的化学物质，而不是只有一个。因此，我们必须将这一祖先分析扩展到多个基因，我们计划同时测试各种基因，以重现“祖先新陈代谢”，从而确定薄荷的祖先可以制造什么化学物质。我们还将试图找出基因在进化过程中在基因组中的位置。随着基因的进化，基因似乎会在基因组中跳跃，我们希望通过比较基因的行为和基因组位置来发现为什么会发生这种情况。所有这些研究将使我们能够回答薄荷何时以及如何获得制造内酯的能力。这反过来将为植物如何制造新的化学物质以及它们的基因和基因组如何进化以适应环境提供更广泛的教训。植物是大自然的绿色化学家：了解植物如何制造有用的化学物质可以帮助我们以环境友好的方式制造我们自己的植物启发的化学物质。

项目成果

Phylogeny-Aware Chemoinformatic Analysis of Chemical Diversity in Lamiaceae Enables Iridoid Pathway Assembly and Discovery of Aucubin Synthase.

• DOI: 10.1093/molbev/msac057
• 发表时间: 2022-04-10
• 期刊: MOLECULAR BIOLOGY AND EVOLUTION
• 影响因子: 10.7
• 作者: Rodriguez-Lopez, Carlos E.;Jiang, Yindi;Kamileen, Mohamed O.;Lichman, Benjamin R.;Hong, Benke;Vaillancourt, Brieanne;Buell, C. Robin;O'Connor, Sarah E.
• 通讯作者: O'Connor, Sarah E.

Ancestral Sequence Reconstruction for Exploring Alkaloid Evolution.

用于探索生物碱进化的祖先序列重建。

• DOI: 10.1007/978-1-0716-2349-7_12
• 发表时间: 2022
• 期刊: Methods in molecular biology (Clifton, N.J.)
• 作者: Lichman BR

Plant biosynthetic gene clusters in the context of metabolic evolution.

在代谢进化的背景下，植物生物合成基因簇。

• DOI: 10.1039/d2np00005a
• 发表时间: 2022-07-20
• 期刊: Natural product reports
• 影响因子: 11.9
• 作者: Smit SJ;Lichman BR
• 通讯作者: Lichman BR

Biocatalytic routes to stereo-divergent iridoids.

• DOI: 10.1038/s41467-022-32414-w
• 发表时间: 2022-08-11
• 期刊: Nature communications
• 影响因子: 16.6

Cell-Free Total Biosynthesis of Plant Terpene Natural Products using an Orthogonal Cofactor Regeneration System.

• DOI: 10.1021/acscatal.1c02267
• 发表时间: 2021-08-06
• 期刊: ACS catalysis
• 影响因子: 12.9
• 作者: Bat-Erdene U;Billingsley JM;Turner WC;Lichman BR;Ippoliti FM;Garg NK;O'Connor SE;Tang Y
• 通讯作者: Tang Y